OBJECTIVES: Proton pump inhibitors (PPIs) are commonly used in children for treating gastroesophageal reflux disease and erosive esophagitis symptoms. However, the safety profile for long-term use of PPIs in children is still largely unclear. The objective of this study was to identify the adverse events (AEs) associated with pediatric PPI use and stratify them by individual PPI, age of patient (child versus infant), and whether the PPI was a primary suspect drug or used with other medications. PPI use has been related to respiratory infections as well as activity-related bone fractures. Children with asthma are much more likely to be treated with a PPI than nonasthmatic children. METHODS: A retrospective, descriptive analysis was conducted. Reports of AEs related to PPIs from 1997 through 2011 for children (aged 1-17 years) and infants (<1 year old) were retrieved from the FDA Adverse Event Reporting System. RESULTS: A total of 112,060 reports were retrieved for children. Of these, 53.8% were for omeprazole, 24.7% for lansoprazole, 9.9% for esomeprazole, 10.1% for pantoprazole, and 1.5% for rabeprazole and dexlansoprazole combined.  There were 14,122 deaths, 9,221 associated with omeprazole. There were 46,046 initial or prolonged hospitalizations. There were 6093 reports of disability. The majority (92,954) of the reports involved concomitant use of a PPI; the PPI was the primary or secondary suspect drug in the remainder of the reports.  There were 3,794 reports retrieved for infants, of which 38.9% were associated with omeprazole and 39.8% with lansoprazole. There were 500 reports of infant deaths, with 236 associated with omeprazole.  There were 1,524 events involving hospitalization. Concomitant use of PPIs accounted for 3198 (84.3%) of the reports. CONCLUSIONS: Pediatric PPI-related AEs involved death, hospitalization, disability, and life-threatening outcomes. Further investigation is warranted. Currently, the FDA recommends that health care providers deliver the shortest, lowest-dose PPI regimen as possible.